The presentation, course and outcome of COVID-19 infection in people with Prader-Willi syndrome: unexpected findings from an international survey

Background Prader-Willi syndrome (PWS), is a genetically determined neurodevelopmental disorder, associated with intellectual disabilities and a high incidence of obesity, diabetes mellitus, and respiratory disorders. We hypothesised that COVID-19, a viral infection which more severely affects people with these conditions, would, in people with PWS, present atypically and result in severe outcomes. Method A structured on-line questionnaire was piloted with parents and professionals at the International Prader-Willi Syndrome Organization (IPWSO) and promoted internationally through their global network. Family members/other carers were asked to complete if someone they cared for with PWS was strongly suspected or confirmed as having COVID-19. Results Over 1 year of the pandemic 72 responses were received, 47 adults, 25 children. The following underlying conditions were present: 16 people with PWS were overweight and 18 obese, five had diabetes mellitus and 18 sleep apnoea. Main presenting symptoms were raised temperature, fatigue/daytime sleepiness, dry cough, headache/pain, and feeling unwell, with illnesses generally lasting less than a week. Length of illness was not significantly related to age, BMI, sex, or genetic subtype. No one was ventilated or in an intensive care unit or died, one person was in hospital for four days needing oxygen. Conclusions Contrary to our hypothesis, the PWS cohort had asymptomatic infection or mild illness. A possible explanation, supported by anecdotal evidence from parents and professional carers, is that people with PWS have a degree of innate immunity to viral infections. However, likely selection effects and a relatively low number of responses means that further evidence is needed to test this hypothesis. Supplementary Information The online version contains supplementary material available at 10.1186/s13023-022-02228-6.


The survey
Please complete this survey after the person has come to the end of their COVID-19 infection, answering as many of the questions as you can to the best of your ability. If you are uncertain about the answers to any specific question do consult with others. The survey will take approximately 15 to 30 minutes to complete and must be completed in one go. Where a written response is required, please write in English if you feel able to or in your own language, we will arrange translation. Keep your answers short using only single words where appropriate. Thank you for your support and understanding.

Consent
The survey is anonymous. The age of the person with PWS and country of residence are requested because these may be important factors in the outcome of their COVID-19 infection. No identifiable information will be available about any individual with PWS. Taking part is entirely voluntary and if you prefer not to do so we understand. A more extensive information sheet is available on our website www.ipwso.org/covid-19 and can be printed if necessary.
If you have any questions, please contact Agnes Hoctor (office@ipwso.org). We appreciate that this survey will be particularly difficult for those family members and/or care staff who were caring for someone with PWS who subsequently passed away. If it is too difficult we understand. If there is someone else who knew the person well who you feel can help do ask them.
Thank you for your help.

Consent
Please indicate that you are willing to complete the survey and that you understand how your answers will be used.
I have understood the reasons for the survey and that I do not have to take part and I understand that by submitting this form I am consenting to taking part in the survey. *

1.
Yes No I understand that the anonymised information provided will be used as set out in the information sheet. *

2.
Yes No I understand that the information collected will not be used to identify the person with PWS affected by COVID-19 and all information is anonymised and will be stored securely. *

3.
Yes No I am a family member/friend/paid carer for the person with PWS who is suspected as having or has been diagnosed as having COVID-19 infection and I have known the person concerned during the period they have been ill. * 4.

No
If it is possible to do so, please ask the person with PWS for their assent/consent to you giving this information. Please explain that the survey is anonymous and that their identity will not be known to IPWSO. Please indicate by selecting the statement that best applies. *

5.
This survey has been explained to the person with PWS and they agree to the survey being completed The person with PWS is too ill at present to ask for their agreement but I believe that they would have agreed if they had been well enough The person with PWS has passed away Other, for example the person is a child/unable to understand the survey The questions below apply to the person with PWS Background about the person and information about the illness Age of the person with PWS. * 6.
Sex of the person with PWS (assigned or self-reported). * 7. Circumstances at the time of the infection (select one only). 20.
Living at home with family members Living in a group setting for people with PWS, with staff support and food security Living in a group setting for people with and without PWS, without or with limited food security Living by themselves with at least daily staff support and food security Living by themselves with minimal support and no food security Other If you selected "Other" above please specify here. 21.
Please indicate if you noticed any of the following signs or symptoms during the COVID-19 illness (select all that apply). If you selected "Other" in the question above please specify here. 23.
Preferably by using the numbers beside the signs and symptoms above in question 22, or by typing the answers in, please list the three most significant early signs or symptoms that you observed which made you concerned that the person with PWS was becoming unwell (e.g, 1, 3, 16).

24.
Preferably by using the numbers beside the signs and symptoms above in question 22, or by typing the answers in, please list the three most obvious signs or symptoms which you observed in the person with PWS during the course of the illness (e.g, 1, 2, 12).

25.
Preferably by using the numbers beside the signs and symptoms above in question 22, or by typing the answers in, please list the three symptoms which the person with PWS most often reported or complained about during the course of the illness (e.g, 7, 10, 11).

26.
This question is for the carers of those people with PWS who were admitted to hospital.
What was the reason for hospital admission (select all that applied)?

Marked deterioration in general health
Not eating and drinking sufficiently The person with PWS was not in hospital (go to question 32) Other Not known If you selected "Other" above please specify here. 28.
If the person with PWS was in hospital which of the following treatments were given (select all that apply)?

29.
Admitted to the intensive care unit in the hospital Given oxygen to breath If you selected "Any other treatments" please specify here. 30.
If the person was on a ventilator in hospital please state for how many days this lasted.

31.
Whether or not the person with PWS was in hospital, what was the outcome of the suspected or proven COVID-19 infection? Which of the following most accurately describe the outcome (select one only)?

32.
Full recovery and back to their normal self Partial recovery but not fully back to their normal self Died as a consequence of COVID-19 infection Died as a result of other complications secondary to  Please indicate as best you can how long the person was ill with possible or diagnosed COVID-19 infection -from first symptoms to recovery or passing away.

33.
Less than one week More than one week but less than two weeks More than two weeks (please specify below) If you selected "More than two weeks" above please specify the length of time here.

34.
For those people with PWS who passed away please answer the following to the best of your ability (otherwise please go to question 38).
What was the direct cause of death as indicated on the death certificate or told to you by a doctor?

35.
Were there any other factors that were listed on the death certificate or told to you by a doctor that may have contributed to the death of the person with PWS?

36.
Were there any other factors that, in your opinion, may have contributed to the death of the person with PWS?

37.
Many countries in the world have placed severe restrictions on people's lives during the pandemic. Please indicate which of the following statements best describes any changes that have taken place in the area where the person with PWS lives (select the one that best applies).

38.
There have been no restrictions and most people are still allowed to lead their normal life There are relatively minor limitations -for example, not mixing with many people at a concert or at a sports event, and keeping their distance from others when out